Reading 3: Association Nuclei of the Thalamus

Question 1

Definition and Function of the specific relay nuclei

Answer 1

• The thalamus is conventionally viewed as a simple relay, conveying sensory information to the cerebral cortex.

Question 2

Lateral geniculate nucleus

Answer 2

• This thalamic nucleus gets its input from neurons in the retina, called retinal ganglion cells, which form the optic nerve. The axon projections from the retina make strong excitatory connections on lateral geniculate neurons which faithfully relay the input firing pattern up to primary visual cortex, the first stage in visual processing in the cerebral cortex.
• There is very little transformation of the information as it passes through the thalamus; the receptive fields of geniculate neurons are almost the same as those of their input retinal ganglion cells. The cortex gets to see the output of the retina with minimal distortion from the thalamus.

Question 3

How do association nuclei differ from relay nuclei?

Answer 3

These nuclei differ from the specific relay nuclei in that most of their inputs come from the cortex itself, and their outputs tend to project to higher order cortical regions.
* i.e., regions of the cortex involved in complex aspects of sensory processing and cognition.
* Together, these observations suggest that the thalamus collaborates with the cerebral cortex rather than merely passing on information.

Question 4

Driver Versus Modulator Inputs

Answer 4

1) Driver Inputs: The driver inputs to the lateral geniculate, for example, are the retinal ganglion cells.
* These inputs make up a small fraction of the synapses on the lateral geniculate neurons, but they form large glutamatergic excitatory synapses on the proximal dendrites of the geniculate neurons.
* Activity of these driver synapses powerfully activates geniculate neurons through ionotropic AMPA-type glutamate receptors.
* Activity of driver inputs is the main cause of action potentials in lateral geniculate neurons. It’s why the geniculate firing pattern follows the retinal firing pattern.
* Other specific relay nuclei of the thalamus have their own specific driver inputs.
* Ie, the medial lemniscus forms the driver input to the ventral posterior lateral and ventral posterior medial nuclei which relay somatic sensory information to primary somatic sensory cortex.

Question 5

Driver versus modulator inputs

Answer 5

2) Modulator inputs come from multiple sources, including the brainstem (e.g., norepinephrine fibers from the locus coeruleus), inhibitory GABAergic inputs from the thalamic reticular nucleus and feedback projections from the cerebral cortex.
* * These modulator inputs account for most of the synapses on thalamic neurons, but they are small synapses on distal dendrites, so the effect of individual modulator synapses is comparatively small.
* Furthermore, (with the exception of the GABAergic inputs, which activate ionotropic GABAA receptors as well as metabotropic GABAB receptors) modulator synapses activate metabotropic G-protein-coupled receptors (GPCRs) on thalamic neurons.

Question 6

Cerebral cortex

Answer 6

• The cerebral cortex is a 2 -4 mm thick sheet of tissue approximately 0.120 square meters in area.
• This sheet is divided into six distinct layers, which are usually numbered from the outside in: the outermost layer is layer 1 and the deepest layer is layer 6.

Question 7

Feedforward projections vs feedback projections in lateral geniculate (LGN)

Answer 7

1) feedforward projections from the lateral geniculate to the cerebral cortex terminate in focused (i.e., the terminals are clustered together) regions of layer 4.
2) modulator feedback projections from the cortex to the lateral geniculate
originate in layer 6.
This is a specific example of a general pattern for specific relay nuclei: feedforward projections from specific thalamic nuclei terminate in layer 4, whereas feedback
projections from the cortex to the thalamus originate in layer 6.

Question 8

What is the function of these feedback modulator connections?

Answer 8

One hypothesis is that they enable the cortex to regulate the flow of information through the thalamus, for example by allowing information to flow through a subset of geniculate neurons while blocking information flow through other geniculate neurons.

In the case of the lateral geniculate, this gating mechanism could contribute to our ability to identify and focus visual attention on a specific object in a visual scene or to extract an identifiable object from an ambiguous input.

Question 9

The thalamus’ role in regulating information flow

Answer 9

• Thalamic neurons can switch between two different types of behavior, called the transmission mode and the bursting mode (Fig. 4).
• A thalamic neuron in the transmission mode fires patterns of action potentials that closely follow the activity of the driver inputs. This mode is thought to be important for accurately relaying sensory and other types of information to the cortex.
• A thalamic neuron in the bursting mode fires a rapid (> 100 hertz) burst of ~6 action potentials, followed by a quiet period lasting for a few hundred milliseconds (Fig 4).
• Repetitive rhythmic bursts of thalamic neurons are characteristic of slow wave sleep.
• Bursts also occur in awake behaving animals. These awake bursts may be a mechanism for “closing the gate” on some thalamic relays, providing way to block some inputs to the cortex while letting others go through, or they may be a wake-up call,
  signaling that something new and important is happening.

Question 10

Association Nuclei of the Thalamus and their differences

Answer 10

• The largest association nuclei of the thalamus are the pulvinar and the medial dorsal nucleus.
• Two important differences between these nuclei and specific relay nuclei like the lateral geniculate are:
  1) association nuclei receive most (though not all) of their driver inputs from the cerebral cortex
  2) their projections to the cerebral cortex are in some cases diffuse (i.e., the terminals are spread out) and terminate in cortical layers other than layer 4.

Question 11

Specific relay nuclei Vs association nuclei

Answer 11

• The image shows the terminals of two different axons, one from a specific relay nucleus and one from an association nucleus.
• The specific relay neuron ends in a tight cluster of presynaptic terminals within
  cortical layer 4. This type of projection is used to convey precise sensory input to the cortex. It enables regions of cortex to form detailed topographic maps, like the retinotopic map of visual space in primary visual cortex or the map of the surface of the body in primary somatic sensory cortex.
• The association neuron, on the other hand projects to multiple different cortical layers and to different regions of cortex. These different types of thalamic projections have been referred to as core versus matrix
  projections. They may not represent distinct categories, but rather two extremes of a continuum.
• Some thalamic nuclei are mostly core, some mostly matrix and some a mixture of the two.

Question 12

Another difference between specific relay and association nucelei.

Answer 12

• The driver inputs to association nuclei come mainly (though not entirely) from the cortex itself. They come from large excitatory neurons, called pyramidal neurons, in cortical layer 5. These projections make powerful excitatory synapses that drive action potentials in association thalamic neurons, which in turn send their axons back to the cortex, in at least some cases through matrix-type connections.
• So, the pulvinar and medial dorsal nucleus enable different regions of cortex to talk to each other, by way of the thalamus.

Question 13

What is the function of the association nuclei??

Answer 13

If one region of cortex wants to talk to another region, why not do it directly, rather than going through the thalamus. Many cortical regions do, in fact, connect both directly and by way of parallel connections through the thalamus. At present, we don’t precisely know the benefit of having two parallel pathways, one in which the thalamus intervenes between cortical areas, but several hypotheses have been proposed:
1) Based on the observation that at least some cortical driver projections to the pulvinar and medial dorsal nucleus are branches of axons that send movement commands to the brainstem and spinal cord. In other words, a copy, called an efference copy, of descending signals that control movement is sent to the association thalamus. According to this hypothesis, this efference copy of motor commands activates association thalamic neurons which then project back to other regions of cortex. This cortico-thalamo-cortical loop might enable one cortical region to broadcast a motor command to other cortical regions, informing them that a self-generated movement is about to happen.
- Every time your eyes makes a saccade, the world moves across your retinas, so the world should seem like it’s constantly moving around. But it doesn’t, in part because when you make a saccade, an efference copy of the saccade command, which comes from an eyecontrol region of the cortex, is sent to other regions of the cortex, perhaps, at least in part, via the thalamus, letting them know that it’s your eyes that are moving, not the world.

2) Another hypothesis is that cortico-thalamo-cortical connections could help transiently bind together activity in different cortical regions. For example, when you see a red car driving down the street, different regions of cortex encode the shape of the car, its identity as a car, its red color and its location
and movement. The neuronal activity in these different cortical regions must be in some way bound together to create the unified perception of a red car driving down the street. This binding could be performed by direct cortico-cortical connections, and in fact these connections do exist; however, routing additional connections through the thalamus might enable it to gate the flow of intracortical
information, so that selected signals (e.g., those aspects of a visual scene you want to pay attention to) are more strongly bound together.